Albumin Infusion in Patients with Cirrhosis: Time for POCUS-Enhanced Physical Examination.
TL;DR: Point-of-care ultrasonography (POCUS) has been used to evaluate the fluid status of patients with suspected hepatorenal syndrome as mentioned in this paper. But, the use of POCUS has not yet been explored in clinical trials.
Abstract: Objective assessment of fluid status is of utmost significance in the management of patients with complex disorders involving hemodynamics and multi-organ crosstalk such as cardiorenal or hepatorenal syndrome. The role of volume expansion using intravenous albumin in the setting of hepatorenal syndrome has been an everlasting debate among clinicians. With the accumulating evidence on the deleterious consequences of iatrogenic fluid overload, empiric albumin administration in these patients has been the focus of much attention, and the findings of recent studies suggest a higher incidence of pulmonary complications with albumin. Poor sensitivity of conventional physical examination has led to an interest in the utility of novel noninvasive bedside tools such as point-of-care ultrasonography (POCUS) to evaluate hemodynamics more precisely. Once confined to specialties such as obstetrics and emergency medicine, the scope of diagnostic POCUS is rapidly expanding in other fields including internal medicine and nephrology. Herein, we offer our perspective on the emerging role of POCUS for objective evaluation of patients with suspected hepatorenal physiology based on our experience. We propose that future clinical trials consider incorporating this strategy and explore the impact of POCUS-guided therapy on the outcomes.
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TL;DR: The third randomized trial based in North America evaluating terlipressin, met its primary end point of showing greater rates of acute kidney injury (AKI) reversal in the terlipressesin arm as mentioned in this paper .
10 citations
TL;DR: In this article, the authors explore the history of regulatory approval for terlipressin in the United States, examine the results from CONFIRM and the concerns they raised and consider the future role of terlipressesin in this critical clinical area of continued unmet need.
10 citations
TL;DR: How nephrologist-performed POCUS has the potential to provide answers to focused questions that the authors encounter in diagnosis and management of patients with AKI is discussed.
Abstract: Acute kidney injury (AKI) is a clinical syndrome caused by a multitude of hemodynamic, toxic, and structural insults to the kidney, and portends worse patient outcomes. Despite careful history taking, physical examination, and analysis of laboratory data, a void is evident in the diagnostic process and clinical monitoring of AKI. Point-of-care ultrasonography (POCUS) is a limited ultrasound study performed by the clinician at bedside as an adjunct to physical examination. Growing body of evidence points to POCUS as a powerful tool in a variety of clinical settings. Herein, we discuss how nephrologist-performed POCUS has the potential to provide answers to focused questions that we encounter in diagnosis and management of patients with AKI. From excluding hydronephrosis to providing real-time insights into hemodynamics, incorporation of POCUS helps integrate all the pieces of patient data and formulate individualized treatment plans. Future studies are needed to evaluate the impact of multi-organ POCUS on AKI-related pragmatic patient outcomes, the potential of this technique to stratify the risk and to identify patients with different levels of severity of AKI and different pathophysiological signatures.
7 citations
TL;DR: In this paper , the authors investigated markers of systemic inflammation, immune function, albumin binding, and cardiovascular function using samples from Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) taken at baseline, day 5, and day 10 of the trial to identify why targeted albumin infusions had no effect in hospitalized patients.
Abstract: INTRODUCTION: Albumin is recommended in decompensated cirrhosis, and studies have shown potential immunomodulatory effects. However, 2 large trials of repeated albumin infusions demonstrated contrasting results between outpatients and hospitalized patients. We investigated markers of systemic inflammation, immune function, albumin binding, and cardiovascular function using samples from Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) taken at baseline, day 5, and day 10 of the trial to identify why targeted albumin infusions had no effect in hospitalized patients. METHODS: Plasma samples were analyzed from 143 patients (n = 71 targeted albumin; n = 72 standard care at baseline) for cytokines, cardiovascular markers, prostaglandin E2, the effect of plasma on macrophage function, and albumin radioligand binding and oxidation status. The sample size was based on our feasibility study, and samples were selected by a trial statistician stratified by the serum albumin level and the presence of infection at randomization and analyses performed blinded to the study arm. Data were linked to 3-month mortality and treatment groups compared. RESULTS: Increased baseline model for end-stage liver disease score, white cell count, calprotectin, CD163, tumor necrosis factor, renin, atrial natriuretic peptide, and syndecan-1 were associated with 3-month mortality. Despite infusing substantially differing volumes of albumin, there were no significant differences in inflammatory markers, albumin–prostaglandin E2 binding, or cardiovascular markers between treatment arms. DISCUSSION: Contrary to many preclinical studies, targeted intravenous albumin therapy in hospitalized decompensated cirrhosis had no effect across a broad range of systemic inflammation, albumin function, and cardiovascular mediators and biomarkers compared with standard care, consistent with the null clinical findings.
4 citations
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TL;DR: This paper elaborate on this possible pathophysiological mechanism of fluid overload, its potential causes and amplifiers, and review its potential Causes and Amplifiers.
Abstract: Although fluid overload is one of the most prominent features of acute heart failure (AHF), its mechanism remains challenging, due to the lack of consistent data from prospective studies. Traditionally, fluid overload was thought to be mainly the result of either increased intake of fluid and salt or non-adherence with diuretic therapy. However, recent data showed little weight change before or during an AHF event suggesting that in many cases fluid overload is caused by other mechanisms such as fluid redistribution and neurohormonal or inflammatory activation. Redistribution may be the result of a combined vascular and cardiac process reducing capacitance in the venous system (and hence increasing preload) and increasing arterial stiffness and resistance (and hence afterload). When these vascular processes occur acutely and are superimposed on reduced cardiac function; fluid is redistributed to the lungs instigating pulmonary congestion. In this paper we elaborate on this possible pathophysiological mechanism and review its potential causes and amplifiers.
293 citations
TL;DR: In the RENAL study, a negative mean daily fluid balance was consistently associated with improved clinical outcomes and may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.
Abstract: Objective: To examine associations between mean daily fluid balance during intensive care unit study enrollment and clinical outcomes in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) replacement therapy study.
Design: Statistical analysis of data from multicenter, randomized, controlled trials.
Setting: Thirty-five intensive care units in Australia and New Zealand.
Patients: Cohort of 1453 patients enrolled in the RENAL study.
Interventions: We analyzed the association between daily fluid balance on clinical outcomes using multivariable logistic regression, Cox proportional hazards, time-dependent analysis, and repeated measure analysis models.
Measurements and main results: During intensive care unit stay, mean daily fluid balance among survivors was -234 mL/day compared with +560 mL/day among nonsurvivors (p < .0001). Mean cumulative fluid balance over the same period was -1941 vs. +1755 mL (p = .0003). A negative mean daily fluid balance during study treatment was independently associated with a decreased risk of death at 90 days (odds ratio 0.318; 95% confidence interval 0.24-0.43; p < .000.1) and with increased survival time (p < .0001). In addition, a negative mean daily fluid balance was associated with significantly increased renal replacement-free days (p = .0017), intensive care unit-free days (p < .0001), and hospital-free days (p = .01). These findings were unaltered after the application of different statistical models.
Conclusions: In the RENAL study, a negative mean daily fluid balance was consistently associated with improved clinical outcomes. Fluid balance may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.
229 citations
TL;DR: It is found that defining severe venous congestion as the presence of severe flow abnormalities in multiple Doppler patterns with a dilated IVC showed the strongest association with the development of subsequent AKI when detected at ICU admission, which outperformed central venous pressure measurements.
Abstract: Organ congestion is a mediator of adverse outcomes in critically ill patients. Point-Of-Care ultrasound (POCUS) is widely available and could enable clinicians to detect signs of venous congestion at the bedside. The aim of this study was to develop several grading system prototypes using POCUS and to determine their respective ability to predict acute kidney injury (AKI) after cardiac surgery. This is a post-hoc analysis of a single-center prospective study in 145 patients undergoing cardiac surgery for which repeated daily measurements of hepatic, portal, intra-renal vein Doppler and inferior vena cava (IVC) ultrasound were performed during the first 72 h after surgery. Five prototypes of venous excess ultrasound (VExUS) grading system combining multiple ultrasound markers were developed. The association between each score and AKI was assessed using time-dependant Cox models as well as conventional performance measures of diagnostic testing. A total of 706 ultrasound assessments were analyzed. We found that defining severe venous congestion as the presence of severe flow abnormalities in multiple Doppler patterns with a dilated IVC (≥ 2 cm) showed the strongest association with the development of subsequent AKI compared with other combinations (HR: 3.69 CI 1.65–8.24 p = 0.001). The association remained significant after adjustment for baseline risk of AKI and vasopressor/inotropic support (HR: 2.82 CI 1.21–6.55 p = 0.02). Furthermore, this severe VExUS grade offered a useful positive likelihood ratio (+LR: 6.37 CI 2.19–18.50) when detected at ICU admission, which outperformed central venous pressure measurements. The combination of multiple POCUS markers may identify clinically significant venous congestion.
175 citations
TL;DR: The terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe as discussed by the authors.
Abstract: Background The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe. Methods We...
147 citations
TL;DR: In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months, and infusion of large amounts of albumin should be cautiously administered in the sickest cirrhosis patients.
146 citations